Hepatitis C is a form of hepatitis caused by a specific virus (Hepatitis C Virus, HCV). In many cases acute hepatitis C has no symptoms and becomes chronic causing long-term damage to the liver; for example cirrhosis and hepatocellular carcinoma. Other associated symptoms may appear in the presence of hepatitis C such as thyroidism, cryoglobulinemia and some types of glomerulonephritis
In particular the term “cryoglobulinemia” refers to the presence in the serum of one or more immunoglobulins (Ig), which precipitate below 37° C. and redissolve on re-warming. Cryoglobulinemia is usually classified into three subgroups: simple cryoglobulinemia (type 1), characterised by the presence of monoclonal Ig, is often associated with haematological diseases and is frequently asymptomatic; mixed cryoglobulinemia or MC (type 2 and type 3) is characterised by the presence of circulating immune-complexes composed of polyclonal IgG, as autoantigens, and of mono-(type 2) or polyclonal (type 3) IgM, as corresponding autoantibodies. MC may be secondary to numerous infections or immunological disorders; when isolated MC may represent a distinct disease, the so-called “essential” MC. Given the striking association (>90%) with HCV infection, the term “essential” is now referred to a minority of MC patients (<5%). HCV may infect the lymphoid tissues and may trigger a mono-polyclonal B-lymphocyte proliferation with different autoantibody production, including the cryoglobulins. MC syndrome is a systemic vasculitis, secondary to the precipitation of circulating immune-complexes and complement in small-sized vessels Clinically, it is characterized by different organ involvement: purpura, skin ulcers, hepatitis, glomerulonephritis, peripheral neuropathy, and/or widespread vasculitis. Some patients may develop a malignancy, usually as late complication, in particular, B-cell non-Hodgkin lymphoma (10%), hepatocellular carcinoma (<5%), or thyroid cancer (<1%).
The first-line treatment of MC should be directed to HCV eradication by interferon and ribavirin; however, this treatment is often unable to eradicate the virus and it may be complicated by important side effects (neuropathy, thyroiditis, etc.). Pathogenetic treatments (plasmapheresis, immunosuppressors, and/or corticosteroids) should be tailored for each patient according to the activity and severity of clinical manifestations. The use of interferon therapy in HCV-related cryoglobulinemic syndrome is based on the assumption that the B-lymphocyte proliferation is virus-dependent and therefore potentially responsive to viral load reduction; so it is not a therapy aimed at the treatment of lymphoproliferations. This therapy with interferon or pegylated-interferon, suitable for increasing the plasmatic half-life of the drug, is also associated with toxicity and side-effects such as: irritability, emotional instability, states of depression, sleep disorders, states of fear, maniacal states, cognition disorders (memory, concentration), confusional states.
It is therefore necessary to find an alternative prophylactic and/or therapeutic therapy for the treatment of the lymphoproliferations briefly described here.
Vaccination with idiotypic Ig has been used for the treatment of B-cell non-Hodgkin lymphoma (NHL), but the notable complexity and high costs involved in producing idiotypic Ig for each patient place significant limits on the application of this vaccination strategy for a large population of subjects.